Certain 3,5-disubstituted 1,2,4-oxadiazole compounds



United States Patent 3,227,725 CERTAIN 3,5-DISUBSTITUTED 1,2,4-0XADIAZOLE COMPOUNDS Fernand Eloy, Reu Lenaers, and Claude Moussebois,

Brussels, Belgium, assignors to Union Carbide Corporation, a corporation of New York No Drawing. Filed Apr. 17, 1962, Ser. No. 188,230 10 Claims. (Cl. 260307) This invention relates to halogenated heterocyclic compounds. In one aspect, this invention relates to halogenated disubstituted oxadiazoles.

The novel compounds which are contemplated in the invention are the 3,5-disubstituted 1,2,4-oxadiazoles where-- in at least one of the two substituents is halogenated. The substitutents can be mono-, po1y-, or per-halogenated. Moreover, the halogens may be situated on the same carbon atom of the substituent or they may be situated on different carbon atoms. These novel compounds can be characterized by the general formula:

or an oxirane group By the term hydrocarbyl, as used herein including the appended claims, is meant a monovalent radical composed solely of carbon and hydrogen and which is free from acetylenic unsaturation, that is alkyl, cycloalkyl, alkenyl, cycloalkenyl and aralkyl.

illustrative hydrocarbyl radicals include alkyl, preferably containing up to 18 carbon atoms, e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, t-butyl, the amyls, the hexyls, the heptyls, the octyls, the dodecyls, the octadecyls and the like; cycloalkyl, preferably containing from to 6 carbon atoms in the cycloalkyl nucleus and up to carbon atoms as a substituted moiety thereof, e.g., cyclopentyl, cyclohexyl, cycloheptyl, 2-propylcyclohexyl, 2-butylcyclohexyl, 2-methylcyclohexyl, and the like; alkenyl, preferably containing up to 18 carbon atoms, e.g., propenyl, l-butenyl, Z-butenyl, 3-butenyl, the pentenyls, the heptenyls, the octenyls, the nonenyls, the octadecenyls, and the like; cycloalkenyl, preferably containing from 5 to 6 carbon atoms in the cycloalkenyl nucleus and up to 10 carbon atoms as a substituted moiety thereof, e.g.,

ice

the cyclopentenyls, the cyclohexenyls, the cycloheptenyls, Z-methylcyclohexen 3 yl, 2-propylcyclohexen-3-yl, 3- rnethylcyclohexen-4-yl, the cyclooctenyls, and the like; and aralkyl, preferably including up to 18 carbon atoms, e.g., phenylbutyl, phenylpropyl, phenylmethyl, naphthylbutyl, naphthylpropyl, naphthylmethyl, anthrylbutyl, anthrylpropyl, anthrylmethyl, and the like.

By the term halohydrocarby as used herein, including the appended claims, is meant the aforesaid hydrocarbyl subsitutents which are halogenated, preferably chlorinated or brominated. In one aspect particularly preferred are the chlorinated lower alkyl substituents, i.e., those containing from one to six carbon atoms, and still more preferred are the polyand per-chlorinated lower alkyl substituents.

Representative groups of halohydrocarbyl substituents are haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, and halogenated aralky.

Typical halohydrocarbyl substituents are chlorornethyl, dichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, trichloromethl, fluoromethyl, difluoromethyl, trifluoromethyl, chloropropyl, polychloropropyl, bromopropyl, polybromopropyl, polyfluoroproyl, chloroethyl, the polychloroethyls, the perchloroethyls, bromoethyl, polybromoethyl, perbromoethyl, perchloropropyl, perbromopropyl, perfluoropropyl, chlorobutyl, bromobutyl, fiuorobutyl, polychlorobutyl, polybromobutyl, polyfiuorobutyl, perchlorobutyl, perbromobutyl, perfiuorobutyl, the chlorohexyls, the polychlorohexyls, the perchlorohexyls, the bromohexyls, the polybromohexyls, the perbromohexyls, the chloroheptyls, the polychloroheptyls, the perchloroheptyls, the bromoheptyls, the polybromoheptyls, the perchloroheptyls, 3-chloro-1-butenyl, 3-bromo-1-butenyl, the chloropentenyls, the bromopentenyls, the chlorocyclohexyls, the polychlorocyclohexyls, the perchlorocyclohexyls, and the like.

By the term haloaryl as used herein, including the appended claims, is meant the halogenated aromatics including the fused and bridged aromatics such as the halogenated phenyls, the halogenated naphthyls, the halogenated anthryls, and the monoand poly-alkyl derivatives thereof which preferably contain up to 6 carbon atoms in the alkyl substituents, The haloaryl substituent is monovalently bonded through an aromatic carbon atom to the oxadiazole nucleus.

Illustrative haloaryl substituents include chlorophenyl, bromophenyl, polychlorophenyl; perchlorophenyl, polybromophenyl, perbromophenyl, fluorophenyl, polyfluorophenyl, perfiuorophenyl, 'chloronaphthyl, bromonaphthyl, fiuoronaphthyl, perchloronaphthyl, perbromonaphthyl, perfiuoronaphthyl, polychloronaphthyl, polybromonaphthyl, polyfluoronaphthyl, chloroanthryl, polychloroanthryl, bromoanthryl, polybromoanthryl, fluoroanthryl, polyfiuoroanthryl, chlorotoly-l, bromotolyl, fluorotolyl, chloroxylyl, bromoxylyl, the polychloroxylys, the polybromoxylyls, perchloroxylyl, perchloroanthryl, perbromoxylyl and the like.

By the term heterocyclic as used herein, including the appended claims is meant heterocyclic substituents which preferably contain from 5 to 6 atoms in the heterocyclic nucleus and preferably still those which contain from 1 to 3 hetero atoms in said nucleus such as nitrogen, oxygen, and sulfur.

The heterocyclic substituents can be bonded directly from the heterocyclic nucleus to the oxadiazole nucleus or through 1 or more carbon atoms, -R N=N=R (wherein R is a divalent saturated aliphatic hydrocarbon, preferably containing from 1 to 6 carbon atoms),

II C (wherein R is a divalent saturated aliphatic hydrocarbon, preferably containing from 1 to 6 carbon atoms), and the like. In addition, the heterocyclic radical can contain up to 10 atoms as a substituted moiety thereof.

Typical heterocyclic substituents include piperidyl, furyl, tetrahydrofuryl, pyrryl, pyranyl, tetrahydrothienyl, thienyl, tetrahydropyranyl, pyridyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, thiadiazolyl, morpholyl, pyrrolidyl, and the like.

By the term acyclic as used herein, including the appended claims are contemplated the monovalent radicals which are composed solely of carbon, hydrogen, and oxygen and which are free from ethylenic, acetylenic, vand benzenoid unsaturation, with the proviso that oxygen is present as an etheric group (O), a carbonyl group an esteric group,

Illustrative acyclic substituents are the alkoxyalkyls, e.g., methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, propoxyethyl, butoxyethyl, methoxypropyl, ethoxypropyl, propoxypropyl, bntoxypropyl, butoxybutyl, and the like; the acylalkyls, preferably the alkanoylalkyls, e.g., the acetylalkyls, the propanoylalkyls, the butanoylalkyls, the pentanoylalkyls, the hexanoylalkyls, and the like; the acyls, preferably the :alkanoyls, e.g., ethanoyl, propanoyl, butanoyl, pentanoyl, hexanoyl, heptan-oyl, octanoyl, and the like; the alkanoyloxyalkyls, e.g., acetyloxymethyl, acetyloxyethyl, acetyloxypropyl, acetyloxybutyl, propanoyloxymcthyl, propanoyloxyethyl, propanoyloxypropyl, propanoyloxybutyl, butanoyloxymethyl, butanoyloxyethyl, butanoyloxypropyl, butanoyloxybutyl, and the like; the vicinal epoxyalkanes, preferably having the oxirane group one carbon atom removed from the oxadiazole nucleus, e.g., 2,3-epoxypropyl, 2,3epoxybutyl, 2,3-epoxypentyl, 4,5-epoxyhexyl, 4,5-epoxyheptyl, 5,6- epoxyoctyl, and the like.

Illustrative of the novel compounds include 3-(alphachloroethyl)-5-methyl-1,2,4-oxadiazole, 5,5 bis(cbloromethyl) 3,3 dioxadiazole, 1,2 bis(5 chloromethyloxadiazolyl)methane, 3 phenyl-S-trichloromethyl-1,2,4- oxadiazole, 1,4-bis(5-chloromethyl oxadiazolyl)butane, azo-N,N bis(3-isopropyl-S-trichloromethyl)oxadiazolyl, 3-( l-methylethyl)-5-trichloromethyl-1,2,4-oxadiazole, 3-methyl-5-trichloromethyl-1,2,4-oxadiazole, 3-methyl-S-dichloromethyl-1,2,4-oxadiazole, 3-methyl-5-chloromethyl-1,2,4-oxadiazole, 3-ethyl-S-trichloromethyl-1,2,4-oxadiazole, 3-gamma-trichloropropyl-S-trichloromethyl-1,2,4-

oxadiazole 3-(t-butyl) -5-trichloromethyl-1,2,4-oxadiazole, 3-(n-nonyl -5-trichloromethyl-1,2,4-oxadiazole, 3-rnethyl-S-tribromomethyl-1,2,4-oxadiazole, 3-allyl-5-trichloromethyl-1,2,4-oxadiazole,

or an oxirane group 3-(cycloheXen-3-ly) -5-trichloromethyl-1,2,4-

oxadiazole,

3- (2,3 -dibromopropyl) -5-trichloromethyl-1,2,4-

oxadiazole,

3 -(4-chlorophenyl) -5-trichloromethyl-1,2,4-

oxadiazole,

3- (4-chlorobenzyl -5-tricl1loromethyl-1 ,2,4-'oxadiazole,

3- S-nitrofuranyl-Z -5-trichloromethyl-l ,2,4-

oxadiazole,

3-(4-pyridyl) -5-trichloromethyl-1,2,4-oxadiazole,

3 -chloromethyl-S-trichloromethyl-1,2,4-oxadiazole,

3-chlorornetl1yl-5-dichloromethyl-1,2,4-oxadiazole,

3- (2-pyridyl) -5-trichloromethyl- 1 ,2,4-oxadiazole, and the like.

Still other illustrative novel compounds are 3-(2-4-dichlorophenyl)-5-(1,1-dichloroethyl)- 1,2,4-oxadiazole, 3-cyclopentyl-S-trichloromethyl-1,2,4-oxadiazole, 3-(2-ethylhexyl -5-dichlorornethy1-1,2,4-oxadiazole, 3-isopropyl-S-dibromomethyl-1,2,4-oxadiazole, 3-methoxymethyl-S-trichlorornethyl-1,2,4-oxadiazole; 1,2-bis(3-trichloromethyl)- 1 ,2,4-oxadiazol-5-yl) ethane; 3 (3 -methyloxadiazol-5-yl) -5-trichloromethyl-1,2,4-

oxadiazole, 3-tert.butyl-S-dichloromethyl-1,2,4-oxadiazole, 3 -(2-ethoxyethyl) -5-dibromochloromethyl-1,2,4-

oxadiazole, 3- 2-cyanoethyl -5-trichloromethyl- 1 ,2,4-oxadiazole, S-(Z-phenylethyl)-3-trichloromethyl-1,2,4-oxadiazole; 3- 8,9-dichloroheptadc cyl -5-trichloromethyl- 1,2,4-oxadiazole, 3- (Z-tetrahydrofuryl) -5-trichloromethyl-1,2,4-

oxadiazole, 3-crotyl-S-bromodichloromethyl-1,2,4-oxadiazole, 3-benzyl-S-trichloromethyl-1,2,4-oxadiazole, 3-( l-acetoxyethyl) -5-trichloromethyl-1,2,4-oxadiazole, 3- 2-furyl -5-chloromethyl- 1 ,2,4-oxadiazole, 3-glycidyl-5-trichloromethyl-1,2,4-oxadiazole, B-(Z-bicyclo [2,2,1]heptyl)-5-trichloromethyl-1,2,4-

oxadiazole, 1,2,-bis S-trichloromethyl- 1 ,2,4-oxadiazol-3-yl) ethane, 5-m-chlorophenyl-3-dichloromethyl-1,2,4-oxadiazole, and 3-acetyl-5-trichloromethyl-1,2,4-oxadiazole.

The novel compounds can be prepared by the several alternative methods discussed below.

In one method the preparation is carried out by contacting, in an inert normally liquid organic vehicle, a substituted hydroxamyl halide, e.g., methyl glyoxalate chloroxime, furohydroxamyl chloride, propyl glyoxalate chloroxime, and the like, with a nitrile, e.g., butyronitrile, trichloroacetonitrile, p-cyanopyridine, and the like, at elevated temperatures, e.g., from about 40 C. to about 150 C., until evolution of hydrogen halides ceases. The reaction is schematically shown below:

The product is recovered by conventional methods such as crystallization filtration, and the like.

In another method, the novel compounds are prepared by contacting, in the presence of an inert normally liquid organic vehicle, a substituted hydroxarnyl halide, e.g., methyl glyoxalate chloroxime, furohyclroxamyl chloride, propylglyoxalate chloroxime, and the like, with an imidoester, e.g., methyl imidonitrofuroate, ethyl imidofuroate, propyl imidofuroate, and the like, at a temperature in the range of from about 0 C. to about C., and in a molar ratio of about 1:2. The contact time can vary from several hours to several days, A preferred reaction 5 time is from about 2 to about 72 hours. This reaction is schematically as follows:

NOH R"O R /CR 5 \X HN/ R"-0\ '-o C-R ROH II II NCR XN-HN The novel oxadiazole is reclaimed from the reaction product in a conventional manner, e.g., by crystallization, filtration, or the like.

A still other method of preparation involves fusing together in a molar ratio of about 1:1 a substituted amidoxime salt or amidoxime, e.g., acetamidoxime, salts of acetamjdoxime, trichloromethyl amidoxime, salts of trichloromethyl amidoxime, furoylamidoxime, salts of furoylarnidoxime, and the like, and a substituted amide, e.g., acetamide, butyramide, trichloroacetamide, 2,3,4-pyridine-carboxamide, and the like. The resulting melt is maintained at a temperature between about 80 C. and 200 C. The compound is formed as follows:

NOH o RC\ 0-3.

NH -HA HzN /O\ '-o N NHiA H20 wherein HA can be a mineral acid or an organic acid. The reaction time can vary from a few minutes to several hours. A preferred reaction time is of the order of about 15 minutes. The novel oxadiazole may be reclaimed from the reaction product by conventional techniques such as recrystallization, sublimation, extraction, and the like.

In addition the novel compounds can be prepared by contacting an amidoxime, e.g., acetamidoxime, trichloromethyl amidoxime, fnroylamidoxime, and the like, with an organic acid anhydride e.g., trichloroacetic anhydride, acetic anhydride, trifiuoroacetic anhydride, and the like. The reaction proceeds by the following route:

NOE

The reactants are initially contacted at about room temperature, e.g., about 20 C. and then heated together to a temperature from about 130 C. to about 140 C. and maintained at this temperature for several hours. The reaction product mixture is then quenched in water and the novel compound reclaimed by extraction with a suitable solvent or by filtration if it is a solid.

A further method of preparation comprises a two-step process involving acylation (suitable acylating agents are propanoyl chloride, butanoyl chloride, butanoyl bromide, and the like) of an amidoxime such as acetamidoxime, 3-methylpyridyl amidoxime, propionamidoxime, and the like, followed by cyclization, the latter reaction being carried out at elevated temperature. schematically the reaction proceeds as follows:

NOH 2R-C +RCOX NO NOH RC/ \CR RC NH; O NHr-HX I II The reactants are contacted in an inert normally liquid organic vehicle. The formed hydrohalide salt is removed by conventional techniques and the remaining acylamidoxime is heated to about C. to C. to efiect cyclization. The novel oxadiazole is then removed by crystallization, filtration, and the like.

The compounds of this invention have been found extremely useful for combination root-knot nematodes which incite distinct galls or knots on the roots of certain plants such as tomato, cucumber, potato, and the like. Extensive field and laboratory testing has been carried out to ascertain the preferred compounds for these applications. These tests indicated that the greatest nematocidal activity was possessed by the 3,5-disubstituted 1,2,4-oxadiazoles having at least one halogenated organic substituent, preferably at least one chlorinated organic substituent.

The effectiveness of an illustrative novel compound of this invention in combating nematodes is demonstrated by the field-test results compiled in Table I.

TABLE I.FIELD CONTROL OF ROOT-KNOT NEMATODE WITH A SUBSTITUTED OXADIAZOLE *Perfect rating, i.e., no root-knots=5.0.

It is readily evident from the test results that the compound of the present invention is more efiective in combating nematodes, since considerably lesser amounts of said compound are more effective or at least as eltectivc as the commercially available nematocides.

In addition, a series of tests was conducted with cucumber plants in which the plants were grown in infested but treated soil and compared against plants grown in untreated infested soil. The average degree of gall formation on the roots of the plants was the basis for ascertaining effectiveness of the nematocide. The effective dose (ED) was then visually rated.

The novel compounds tabulated below were tested for their efiectiveness as nematocides, the effectiveness being gauged by pounds of compound required per acre to limit root-damage to cucumber plants to light galling when grown in nematode infested soil (rating: ED

TABLE II.TOXICITY OF SUBSTITUTED OXADIAZOLES TO ROOT-KNOT NEMATODE Pounds per acre Test compound; required for EDa TABLE IICntinued 3-n-heptadecyl-5-trichloromethyl 1,2,4 oxadiazole 38 3,5-bis(chloromethyl)-1,2,4-oxadiazole 12 3-chloromethyl-5-dichloromethyl-1,2,4 oxadi azole 5 3-chloromethyl-5-trichlor0methyl-1,2,4 oxadiazole 5 5-chloromcthyl-3-trichloromethyl-1,2,4 oxadiazole 15 5-chloromethyl-3-dichloromethyl-1,2,4 oxadiazole 2S 3,5-bis(dichloromethyl)-1,2,4-oxadiazole 3-dichloromethyl-5-trichloromethyl-1,2,4 oxadiazole 12 5-dichloromethyl-3-trichloromethyl-1,2,4 oxadiazole 1O 3-allyl-S-trichloromethyl-1,2,4-oxadiazole 1O 3-(3,3,3-trichloropropyl) 5 trichloromethyl- 1,2,4-oxadiazole 5 3-(1-acetoxyethyl)-5 trichloromethyl 1,2,4

oxadiazole 12 3-(4-chlorophenyl)-5 trichloromethyl 1,2,4

oxadiazole 19 3-(4-chlorobenzyl)-5 trichloromethyl 1,2,4

oxadiazole 15 3-(2-pyridyl)-5-trichlorornethyl-1,2,4 oxadi azole 8 3-(4-pyridyl)-5-trichloromethyl 1,2,4 oxadiazole 1O 3-(2-nitrofuranyl-5)-5-trichloromethyl 1,2,4

oxadiazole 19 3-(5-trichloromethyl-1,2,4 oxadiazolyl-3)pyridine hydrochloride 6 Bis(5-chloromethyl-1,2,4-oxadiazolyl-3) 75 3-(5-trichloromethyl-1,2,4 oxadiazolyl 3)-5- trichloromethyl-1,2,4-oxadiazole 75 Bis(5 trichloromethyl 1,2,4 oxadiazolyl-3)- methane 5 1,2-bis(3-trichloromethyl 1,2,4 oxadiazolyl- 5)ethane 10 1,4-bis(S-trichloromethyl 1,2,4 oxadiazolyl- 3)butane 75 1,8-bis(3-trichloromethyl 1,2,4 oxadiazolyl- 5)octane 75 In addition, several of the novel oxadiazoles were tound to possess also other biological activity. For example, 3- trichloromethyl-S-methyl-1,2,4-oxadiazole possesses significant systemic and soil fungidical activity as well as a specific systemic insecticidal activity.

The novel disubstituted 1,2,4-oxadiazoles are also useful as plasticizers for polyvinyl chloride and nylon. Relative- 1y small quantities of such plasticizer impart desirable physical properties to the polymers. For example, a typical formulation comprising 64.5 parts by weight polyvinyl chloride resin, 1.5 parts by weight stabilizer (a barium and cadmium laurate mixture), and 34.0 parts by weight of 3-methyl-S-trichloromethyl-1,2,4-oxadiazole was milled for about 5 minutes at about 158 C. The resulting sheets were almost colorless and flexible, which is indicative of the plasticizing properties of the oxadiazole. Moreover, these oxadiazoles are useful as flame retardants per se.

Furthermore, 1,2,4-oxadiazoles having at least one ethylenically unsaturated substituent, for example, the 3- alkenyl-S-haloalkyl-1,2,4-oxadiazoles, are useful as monomers for vinyl polymerization with other monomers such as butadiene, isoprene, and the like, to yield useful vpolymeric products.

The methods for preparing the hereinabove disclosed compounds will now be further illustrated by the followin g examples.

EXAMPLES IIV Preparation of 3-metlzyl-S-lricltloromethyl-I,2,4- oxads'azole and similar compounds Acetamidoxime (0.1 mole, 7. 4 grams) was added in small portions to trichloroacetic anhydride (0.25 mole, 77.25 grams). During the addition the temperature of the resulting mixture did not exceed 30 C. After dissolution the resulting mixture was heated to about 130 C. and maintained thereat for a time period of about one hour. Thereafter the resulting reaction product mixture was cooled and poured into water contained in a separatory funnel whereby an aqueous phase and an organic phase formed. The phases were separated and .the acqueous phase extracted three times with diethyl ether. The resulting ethereal solution was washed with water, then with an aqueous solution of sodium bicarbonate until evolution of carbon dioxide ceased, again with water, then dried by means of sodium sulfate and subsequently concentrated by evaporating some of the diethyl ether.

The organic phase was subjected to a similar treatment, i.e., washed with water, then an aqueous sodium bicarbonate solution, and again with water. The concentrated ethereal solution obtained from the aqueous phase was then combined with the treated organic phase.

The resulting solution then was subject to distillation under reduced pressure, i.e., about 2 mm. of Hg. Fourteen grams of distillate having a boiling point of 54 C. at a pressure of 5 mm. of Hg was obtained. The distillate was identified as 3-rnethyl-S-trichloromethyl-1,2,4- oxadiazole. The actual yield was of the theoretical yield.

In an analogous manner as above, three additional novel oxadiazoles were prepared. The pertinent data are set forth in Table III below.

TABLE III Percent Example product Temp. 0. Vehicle Time Yield in N0. percent Amidoxime Anhydride 3,5-di-(trichloromethyl)-1,2,4- Trichl0r0acet Trichl0roaectic None 1 hour 61 ii i 'd n1 l5t hl Phth limid 3 t aami o -e -r1c oroa ofngthyl-l,2,4-oxadiz ole propyl- Trichloroacetim. Bli of t Xylene 3hours 64 so vcn B-trichloromethyl-5-methyl-l,2,4- Trichloroacet-n- Acetic 13.1. of Acetic 40 min, at 100 oxadiazole. solvent. anhydride. B.P. of V0 hicle-l-84 hours at room temp A colorless liquid, soluble in organic solvcntr and insoluble in water; boiling point 79.7 C. at 0.5 mm. Hg.

A colorless crystalline compound, soluble in methyl alcohol and insoluble in water, melting point C. A colorless crystalline compound, soluble in organic solvcntl and insoluble in water; melting point. 55 C.

A mixture of oxamidedioxime (0.5 mole, 59 grams) and trichloroacetic anhydride (2.2 moles, 679 grams) l Analysis.Calculated: C, 31.43%; H, 3.07%; N, 12.02%. Found: C, 31.38%; H, 3.14%; N, 13.01%.

EXAMPLE XI was heated to l30140 C. and maintained at this tem- P'epamtwn of Pyrldy!) 5 t'lchlommethyl perature for 3 hours. The mixture was then poured on 4'oxadmzole ice and neutralized with a saturated solution of NaHCO The resulting crystalline product was filtered off, washed with water and recrystallized from ethyl alcohol. The Z 2(OC13C 0)20 crystalline product was identified as bis(5-trichloromethyl- C 1,2,4-oxadiazolyl-3) obtained in a 85% yield. Its melt- N ing point was 142 C. O

In an analogous manner as above additional novel oxadiazoles containing two oxadiazole rings were prefi fi I 3091300011 pared. The pertinent data are set forth in Table IV N C\ below. N

TABLE IV 7 Percent Exlazmple Product p- Vehicle Time Yield in Dioxime Anhydride percent VI 1,l-bis(5-trichloromethyl-oxadiazolyl)- Dimalonamide- Trich10r0acetic- A at room Benzene 3hours 71 methane. mp.

1 h. 50 0. 2 h. reflux. VII 1,l-bis1(5-t1; iflu0romethyl-oxadiazolyl)- Dimalonamide- Trifluoro ce ic Roomtemp. None 53 me 8.116 VIII Azo-N,N-bis-(3isopropyl-5-trichl0ro- Azo-N,N'-bis Trichloroacetic" 13.1. of Benzene 2l1ours methyl-oxadiazolyl). (istabsityrasolvent.

A colorless crystalline compound, soluble in organic solvents and insoluble in water; melting point 86 0. A colorless crystalline compound, soluble in organic solvents and insoluble n Water; melting point 24 C. "A colorless crystalline compound, soluble in organic solvents and insoluble 1n water; melts and decomposes 111 C.

EXAMPLE DC Preparation of 1,4-bz's(S-trichloromethyloxadiazolyl) -n-bulane Adipamidedioxime (0.2 mole, grams) and trichloroacetic anhydride (0.88 mole, 270 grams) were heated together for 3 hours at a temperature of about 130-l40 C. The resulting dark-colored product mixture was poured on ice, neutralized with NaHCO and filtered. Eighty grams of a crystalline product were obtained upon filtration and identified as l,4-bis(5-trichloromethyloxadiazolyl)-n-butane. The yield was 83%. The thus obtained crude oxadiazole was dissolved in hexane and filtered. The solvent was evaporated in vacuo and the resulting crystals were dissolved in a water-ethanol solution and recrystallized. Melting point of the recrystallized compound was 55 C.

EXAMPLE X Preparation of S-isopropyl-S-trichloromethyl- 1,2,4-oxadz'az0le CH H 0 0 a u C NOH+ 01:00 20 --r Chic-([3 Ifil /OH3 CH; C NCCH N Hz CH3 To trichloroacetic anhydride (0.3 mole, 92.7 grams) was added dropwise, with stirring Z-methyl-propamidoxime (0.15 mole, 15.1 grams) so that the temperature remained at 40 -50 C. When the addition was complete the reaction mixture Was heated at about 120 C. for one hour and then poured into ice water. This mixture was then stirred and thoroughly extracted with methylene chloride. These extracts were dried with potassium carbonate, filtered, and subsequently distilled to yield about 23 grams of a water-white liquid, B.P. 5960 C. at 2 mm. of Hg, containing a small amount of solid. Filtration and redistillation resulted in 21 grams (74% yield) of a clear liquid having a boiling point of about 48 49 C. at 1 mm. of Hg. This liquid was identified as 3-isopropyl-S-trichloromethyl-1,2,4-oxadiazole.

2-picolinamidoxime (0.1 mole, 13.7 grams) was added in small portions to trichloroacetic anhydride (0.2 mole, 62 grams). The resulting mixture was heated to 110 C. for 1 hour and poured into cold water. The reaction product was extracted with methylene "chloride, washed with water, with a sodium bicarbonate solution, again with water and dried over calcium chloride. From the extract methylene chloride was evaporated and the residue was distilled at a temperature of about 148-160 C. and at about 2 mm. of Hg pressure. The distillate was crystallized from methanol/water solution and was identified as 3-(2-pyridyl)-5-trichloromethyl-1,2,4-oxadiazole. Its boiling point was 4445 C. and its yield was 18 grams (67%).

EXAMPLE XII Preparation of 3-gamma-trichl0ropr0py l-5-trz'chl0r0- methyl-1,2,4-oxzrd1'a1ole I ll I l CCH2CHzOCl 30 0130 0 OH Gamma trichlorobutyrarnidoxime (0.1 mole, 20.5 grams) was added in small portions to trichloroacetic anhydride (0.2 mole, 62 grams). The mixture was heated for 20 minutes at -110 C. and then poured onto crushed ice. An aqueous phase and an organic phase were formed. The organic phase was extracted with methylene chloride, washed with water, sodium bicarbonate solution and again with water and dried with anhydrous sodium sulfate. The methyelne chloride then was evaporated and the resulting residue fractionated in vacuo. The fractionation yielded 26.2 grams of 3-garnmatrichloropropyl-S-trichloromethyl-1,2,4-oxadiazole which had a boiling point of 112 C. at 0.4 mm. of Hg pressure. The yield was 40% Propionamidoxime (22 grams) and trichloroacetic anhydride (154 grams) were processed according to the technique used for the preparation of compound of Example VI. 20 grams of 3-ethyl-5-trichloromethyl-1,2,4oxadiazole was obtained (35% yield based on the propionitrile used for the preparation of the amidoxime); having a 'boil- H ing point of 39 C. at 0.5 mm. of Hg pressure.

Analysis.Calculated: C, 27.85%; H, 2.32%; N, 13.00%. Found: C, 28.34%; H, 2.50%; N, 12.69%.

EXAMPLE XIV Preparation of 3-m0nochloromethyl-5-trichl0romethyl- 1,2,4-xadiaz0le Monochlor-oacetamidoxime (0.139 mole, grams) was added in small quantities to trichloroacetic anhydride (0.278 mole, 88.5 grams) under cooling.

The mixture was heated to 100-1l0 C. and maintained at this temperature for 4 hours. The resulting brown solution was poured onto crushed ice. An aqueous phase and an organic phase were formed. The organic phase was separated, dissolved in diethyl ether, washed first with an aqueous sodium bicarbonate solution, then with water and finally dried with sodium sulfate. The diethyl ether was then evaporated and the residue was dissolved in petroleum ether, and filtered in order to remove small quantities of amides. Petroleum ether was then evaporated from the solution and the residue fractionated. Fractionation yielded 19.2 grams of S-monochloromethyl-S-trichloromethyl-1,2,4 oxadiazole which had a boiling point of 66.5 C. at 1.5 mm. of Hg pressure. The yield was 61 Analysis.Calcu1ated: C, 20.18%; H, 0.85%; N, 11.88%. Found: C, 20.33%; H, 0.94%; N, 12.03%.

EXAMPLE XV Preparation of 3-m0n0chloromethyl-S-dichloromethyl- 1 ,2,4-0xadiaz0le NOH ClCH2C\ Starting with monochloroacetamidoxime (0.139 mole, 15 grams) and dichloroacetic anhydride (0.278 mole, 66.3 grams) exactly the same technique was followed as for the preparation of Example VIII. 20.8 grams of 3- monochloromethyl-S-d-ichloromethyl 1,2,4 ox-adiazole was obtained. It had a boiling point of 6264 C. at 0.7 mm. of Hg pressure. The yield was 74.5%.

12 Analysis.Calcul-ated: 23.82%; H, 1.48%; N, 13.89%. Found: C, 23.54%; H, 1.52%; N, 14.12%.

EXAMPLE XVI Preparation of 3-(t-butyl) -5-trichl0r0methyl- 1,2,4-0xadiaz0le To trichloroacetic anhydride (0.2 mole, 65 grams) in a 200 ml. Erlenmeyer flask, fitted with -a condenser (protected by a drying tube) and a stirring bar, was added, with stirring, portionwise, pivalamidoxime (0.1 mole, 11.6 grams) at such a rate that the temperature remained between 35 and 45 C. The resulting mixture was then maintained at 130140 C. for one hour and then poured over ice-water mixture. An aqueous phase and an organic phase were formed. The organic phase was extracted with 3 X ml. of methylene chloride, the extract dried with N a 50,; and then filtered and distilled to give 14.6 grams of colorless liquid having a boiling point of 57 C. at 0.8-0.9 mm. of Hg pressure. This liquid was identified as 3-(t-buty1)-5-trichloromethyl-1,2,4 oxadiazole. Its yield was 61%.

Analysis.Calculated for C H Cl N 0: C, 34.52; H, 3.72; N, 11.51. Found: C, 34.87; H, 3.88; N, 11.55, 11.79.

EXAMPLE XVII Preparation of 3-(cycI0hexen-3-yl)-5-trichl0r0methyll,2,4-0xadiaz0le In a manner analogous to Example X 3-(cyelohexen- 3-yl)amidoxime is reacted with trichloroacetic anhydride to give 3-(cyclohexen-3-yl)-5-trichloromethyl-1,2,4-oxadiazole.

Analysis.-Calculated: C, 23,82%; H, 1.48%; N,

13.89%. Found: C, 24.11%; H, 1.49%; N, 14.12%.

EXAMPLE XVIII Preparation of 3-phenyl-S-trichloromethyl-1,2,4- oxadiazole lfiTOH zwhooono O C1sC([) lfil' rio- 3CClaO 0 OH Benzamidoxime (13.6 grams, 0.1 mole) was added gradually to trichloroacetic anhydride (77.2 grams 0.25 mole). After addition the resulting mixture was heated to about -140 C. for about one hour. The resulting reaction product mixture was then poured over crushed ice. An aqueous phase and an organic phase were formed. The organic phase was extracted with diethyl ether. The resulting extract was washed with water, with an aqueous sodium bicarbonate solution, and again with water. The extract was then dried with sodium sulfate and part of the diethyl ether evaporated. The remaining liquid was fractionated and 14 grams of the oxadiazole was obtained. This corresponded to a 70% yield. The compound was observed to have a boiling point of 54 C. at 5 mm. of Hg.

The foregoing discussion and accompanying examples have been intended for illustrative purposes only. Additional embodiments within the scope of this invention will readily present themselves to one skilled in the art.

We claim: References Cited by the Examiner 1. 3-(1-methy1ethyl) 5 trich1oromethy1-1,2,4-oxadi- FOREIGN PATENTS azole.

2. 3-methy1-5-trichloromethyl-1,2,4-oxadiazole. 626470 7/1949 Great Bntam' 3. 3-methyl-5-dichloromethyl-1,2,4-oxadiazole. 5 OTHER REFERENCES Y Y A- Bergmann et a1.: Chem. Abstracts, vol. 48, col. 1361 5. 3-ethyl-5-trich1o1'omethy1-1,2,4-oxadiazole. (195-4).

6. 3-gamma-trich1oropropy1 5 trich1oromethy1-1,2,4- Merck: Chem. Abstracts, Vol. 42, page 4577 (1949). oxadiazole. (1954).

7. 3 chloromethyl-S-trichloromethyl-1,2,4-oxadiazole. 10 P613220 6t Phafm- Chem 4, PP-

s. 3-methy1-5-tribromomethy1-1,2,4-oxadiazole. 367 (1961)- 9. 3-methyl-5-tribromomethy1-1,2,4-oxadiazole. NICHOLAS S RIZZO, Primary Examiner.

10. 3-allyl-5-trichloromethyl-1,2,4-oxadiazo1e.

DUVAL T. MCCUTCHEN, Examiner. 

1. 3-(1-METHYLETHYL) - 5 - TRICHLOROMETHYL-1,2,4-OXADIAZOLE. 